Serotonin transporter promoter polymorphism influences topography of inhibitory motor control

The prefrontal cortex participates in motor control and is modulated by serotonergic activity. The serotonin transporter (5-HTT) is a major regulator of serotonergic neurotransmission and may thus influence motor control. The short allele (s) of the 5-HTT linked polymorphic region (5-HTTLPR) is associated with less 5-HTT expression and function than the long variant (l). The neurophysiological parameters termed 'Go- and NoGo- centroid location' represent characteristic brain electrical substrates of the execution and inhibition of motor response elicited by the Continuous Performance Test (CPT). In the present study, the impact of the 5-HTTLPR genotype on the centroid locations was investigated in 23 healthy subjects. The NoGo-centroid, but not the Go-centroid, was located significantly more anteriorly in the short allele group (mean electrode location in s/s and s/l, 2.86+/-0.37) compared to the group with two long alleles (l/l, 3.34+/-0.49; t=2.66, p<0.05). Age, gender, and test performance did not differ between groups. The results indicate that 5-HTTLPR genotype dependent 5-HTT function is associated with the neurophysiologically assessed topography of inhibitory motor control and provides further evidence for a genetic influence on central serotonergic and motor function.